Department of Chemical and Biological Engineering, University of Wisconsin-Madison , 1415 Engineering Drive, Madison, Wisconsin 53706, United States.
Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, Wisconsin 53706, United States.
J Am Chem Soc. 2017 Dec 27;139(51):18536-18544. doi: 10.1021/jacs.7b08367. Epub 2017 Dec 13.
We explore how two nonionic polar groups (primary amine and primary amide) influence hydrophobic interactions of neighboring nonpolar domains. We designed stable β-peptide sequences that generated globally amphiphilic (GA) helices, each with a nonpolar domain formed by six cyclohexyl side chains arranged along one side of the 14-helix. The other side of the helix was dominated by three polar side chains, from β-homolysine (K) and/or β-homoglutamine (Q) residues. Variations in this polar side chain array included exclusively β-hLys (GA-KKK) and β-hLys/β-hGln mixtures (e.g., GA-QKK and GA-QQK). Chemical force measurements in aqueous solution versus methanol allowed quantification of the hydrophobic interactions of the β-peptide with the nonpolar tip of an atomic force microscope (AFM). At pH 10.5, where the K side chain is largely uncharged, we measured hydrophobic adhesive interactions mediated by GA-KKK to be 0.61 ± 0.04 nN, by GA-QKK to be 0.54 ± 0.01 nN, and by GA-QQK to be 0 ± 0.01 nN. This finding suggests that replacing an amine group (K side chain) with a primary amide group (Q side chain) weakens the hydrophobic interaction generated by the six cyclohexyl side chains. AFM studies with solid-supported mixed monolayers containing an alkyl component (60%) and a component bearing either a terminal amide or an amine group (40%) revealed analogous trends. These observations from two distinct experiment systems indicate that proximal nonionic polar groups have pronounced effects on hydrophobic interactions generated by a neighboring nonpolar domain, and that the magnitude of the effect depends strongly on polar group identity.
我们探讨了两个非离子极性基团（伯胺和伯酰胺）如何影响相邻非极性结构域之间的疏水相互作用。我们设计了稳定的β-肽序列，这些序列生成了全局两亲性（GA）螺旋，每个螺旋都有一个由六个环己基侧链组成的非极性结构域，这些侧链沿 14 螺旋的一侧排列。螺旋的另一侧主要由三个极性侧链组成，来自β-同赖氨酸（K）和/或β-同谷氨酰胺（Q）残基。这种极性侧链排列的变化包括纯β-hLys（GA-KKK）和β-hLys/β-hGln 混合物（例如，GA-QKK 和 GA-QQK）。在水溶液与甲醇中的化学力测量允许定量测量β-肽与原子力显微镜（AFM）的非极性尖端之间的疏水相互作用。在 pH 10.5 下，K 侧链主要不带电荷，我们测量到 GA-KKK 介导的疏水黏附相互作用为 0.61 ± 0.04 nN，GA-QKK 为 0.54 ± 0.01 nN，GA-QQK 为 0 ± 0.01 nN。这一发现表明，用伯酰胺基（Q 侧链）取代胺基（K 侧链）会削弱六个环己基侧链产生的疏水相互作用。含有烷基成分（60%）和带有末端酰胺或胺基成分（40%）的固载混合单层的 AFM 研究揭示了类似的趋势。这两个不同实验系统的观察结果表明，相邻非极性结构域产生的疏水相互作用受近位非离子极性基团的显著影响，并且影响的大小强烈依赖于极性基团的特性。
